Inclusion Criteria

DISEASE CHARACTERISTICS:

- Histologically or cytologically confirmed adenocarcinoma of the colon or rectum

- Locally advanced (unresectable) or metastatic disease

- Patients with resected primary tumors who have documented metastases are
eligible

- Separate histological or cytological confirmation is not required from
patients with a history of colorectal cancer (previously treated by
surgical resection) who have now developed radiological or clinical
evidence of metastatic disease, unless 1 of the following is true:

- An interval of > 5 years has elapsed between the primary surgery and
the development of metastatic disease

- The primary cancer was stage I

- Patient must have a wildtype K-ras gene determined by the SWOG Solid Tumor Repository
laboratory or by local CLIA-certified laboratory

- Patients with a mutation in the K-ras gene not allowed

- The intent of this treatment must be indicated as follows:

- Palliative or neoadjuvant treatment with the potential for resection of all
sites of metastatic disease

- At least 1 paraffin block of previously resected primary tumor or tumor deposit
available

- Patients must have a wildtype K-ras gene

- No known CNS metastases or carcinomatous meningitis

PATIENT CHARACTERISTICS:

Performance status

- ECOG 0-1

Life expectancy

- Not specified

Hematopoietic

- Granulocyte count ≥ 1,500/mm^3

- Platelet count ≥ 100,000/mm^3

- Hemoglobin ≥ 9.0 g/dL (transfusion allowed)

- No history of significant bleeding episodes (e.g., hemoptysis or upper or lower
gastrointestinal bleeding) within the past 6 months unless the source of bleeding has
been resected

Hepatic

- Bilirubin ≤ 1.5 mg/dL

- Albumin ≥ 2.5 g/dL

- No evidence of Gilbert's syndrome for patients assigned to receive FOLFIRI
chemotherapy

- Gilbert's syndrome allowed for patients assigned to receive FOLFOX chemotherapy

Renal

- Creatinine ≤ 1.5 times upper limit of normal

- Protein < 1+ by urinalysis

- Protein < 1 g by 24-hour urine collection for patients with protein ≥ 2+ by
urinalysis

Cardiovascular

- No arterial thromboembolic events within the past 6 months, including any of the
following:

- Myocardial infarction

- Transient ischemic attack

- Cerebrovascular accident

- Unstable angina or angina requiring surgical or medical intervention

- No uncontrolled hypertension (i.e., blood pressure ≥ 160/90 on a regimen of
antihypertensive therapy)

- No New York Heart Association class II-IV congestive heart failure

- No clinically significant peripheral artery disease (i.e., claudication on less than
1 block)

Pulmonary

- No interstitial pneumonia

- No extensive or symptomatic interstitial fibrosis of the lung

- No pleural effusion or ascites that causes ≥ grade 2 dyspnea

Gastrointestinal

- No gastrointestinal perforation within past year

- No uncontrolled, predisposing colonic or small bowel disorder (i.e., > 3 watery or
soft stools daily for patients without a colostomy or ileostomy)

- Patients with a colostomy or ileostomy are eligible at the discretion of the
investigator

Neurologic

- No sensory peripheral neuropathy ≥ grade 2 for patients assigned to receive FOLFOX
chemotherapy

- No uncontrolled seizure disorder

- No active neurological disease

Other

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception during and for at least 2-6 months
after completion of study treatment

- No serious nonhealing wound, ulcer, or bone fracture

- No known hypersensitivity to Chinese hamster ovary cell products or recombinant human
or murine antibodies

- No other malignancy within the past 5 years except adequately treated basal cell or
squamous cell skin cancer or carcinoma in situ of the cervix

PRIOR CONCURRENT THERAPY:

Biologic therapy

- No prior agents that target vascular endothelial growth factor (VEGF) or EGF
receptors including protein products, monoclonal antibodies, or antisense therapies

- No prior bevacizumab or cetuximab

- No concurrent prophylactic filgrastim (G-CSF), pegfilgrastim, or sargramostim
(GM-CSF)

Chemotherapy

- See Radiotherapy

- More than 12 months since prior adjuvant chemotherapy (≤ 6 months in duration) that
included fluorouracil alone or in combination with oxaliplatin or irinotecan
hydrochloride

- No prior regional chemotherapy (e.g., hepatic arterial infusion)

- No other concurrent chemotherapy

Endocrine therapy

- No concurrent hormonal therapy except steroids for adrenal failure, hormones for
noncancer-related conditions (e.g., insulin for diabetes), or intermittent
dexamethasone as an antiemetic

Radiotherapy

- Prior radiotherapy with radiosensitizing chemotherapy allowed

- Prior standard adjuvant chemoradiotherapy for rectal cancer allowed

- At least 4 weeks since prior radiotherapy

- No prior radiotherapy to > 25% of bone marrow

- No concurrent palliative radiotherapy except whole brain irradiation for documented
CNS disease

Surgery

- See Disease Characteristics

- At least 4 weeks since prior major surgery

- At least 2 weeks since prior minor surgery

- Insertion of a vascular access device is not considered a prior surgery

- Recovered from all prior surgery

Other

- At least 4 weeks since prior itraconazole or ketoconazole

- No prior tyrosine kinase inhibitor therapy

- No prior systemic treatment for advanced or metastatic colorectal cancer

- No concurrent aprepitant

- Concurrent full-dose anticoagulation (i.e., warfarin) allowed provided all of the
following criteria are met:

- In-range INR (usually 2-3) on a stable dose of oral anticoagulant or stable dose
of low molecular weight heparin

- No active bleeding

- No pathological condition with a high risk of bleeding (e.g., tumor involving
major vessels or known varices)

- Concurrent antiplatelet agents allowed

- Concurrent daily prophylactic aspirin or anticoagulation for atrial fibrillation
allowed