Inclusion Criteria:

- Must consent to be in the study and must have signed and dated IRB-approved consent
forms conforming to federal and institutional guidelines for the pre-entry tumor
sample submission for central K-RAS testing and for the study treatment

- Must have an ECOG performance status of 0, 1, or 2

- Must have metastatic CRC

- The CRC tumor or metastatic tumor must be K-RAS wild-type as determined by central
testing

- Must be documented disease progression during first-line therapy containing both
oxaliplatin and bevacizumab

- Most recent treatment regimen must have ended ≥ 21 days prior to randomization, and
clinically significant side effects associated with previous therapy must have
resolved to ≤ grade 1 with the exception of neuropathy which must have resolved to ≤
grade 2

- Imaging of the chest, abdomen and pelvis with CT scan or MRI must be performed within
3 weeks prior to randomization

- Must have measurable disease, defined as at least one lesion outside a previous RT
field that can be accurately measured in at least one dimension as ≥ 20mm with
conventional techniques or as ≥ 10mm with 5mm cuts using a spiral CT scan

- Evidence of adequate bone marrow function: ANC ≥ 1200/mm3, hemoglobin ≥ 9g/dL,
platelets ≥ 100,000/mm3

- Evidence of adequate hepatic function. If no liver metastases: AST ≤ 2.5 x ULN, total
bilirubin ≤ 1.5 x ULN for the lab. In the presence of liver metastases: AST ≤ 5.0 x
ULN, total bilirubin ≤ 1.5 x ULN for the lab

- Serum creatinine must be ≤ 1.5 x ULN for the lab

- Must have a fasting blood glucose < 126mg/dL. Fasting is defined as no caloric intake
for at least 8 hours

Exclusion Criteria:

- Life expectancy less than 12 weeks

- Diagnosis of anal or small bowel carcinoma

- Tumor that is considered by the surgeon to be amenable to complete resection

- Previous radiation therapy to > 25% of bone marrow

- Radiation therapy to sites of measurable disease chosen as target lesions

- Radiological evidence and/or clinical signs or symptoms of CNS metastases

- Any of the following conditions and events: uncontrolled hypertension, defined as
systolic BP > 150mmHg or diastolic BP > 100 with or without antihypertensive
medication (patients with hypertension that is well-controlled on medication are
eligible); unstable angina within 6 months before randomization; NYHA Class III or IV
cardiac disease; myocardial infarction within 6 months before randomization;
symptomatic arrhythmia; CNS cerebrovascular ischemia (TIA or stroke) within 6 months
before randomization

- Other malignancies unless the patient is considered to be disease-free and has
completed therapy for the malignancy ≥ 12 months prior to randomization. Patients
with the following cancers are eligible if diagnosed and treated within the past 12
months: carcinoma in situ of the cervix, colon carcinoma in situ, melanoma in situ,
and basal cell and squamous cell carcinoma of the skin

- Serious or non-healing wound, skin ulcers, or bone fracture

- Any significant bleeding unless the source of bleeding has been resected

- History of bleeding diathesis or coagulopathy (patients on stable anticoagulant
therapy are eligible)

- Any evidence of active infection

- Active inflammatory bowel disease

- Grade 3 or 4 diabetes mellitus as defined by NCI's CTCAE v 3.0 pancreatic endocrine:
glucose intolerance (patients with diabetes controlled with diet and/or oral
medications are eligible)

- Symptomatic interstitial pneumonitis or definitive evidence of interstitial
pneumonitis described on CT scan or chest x-ray in asymptomatic patients

- Any other serious concomitant medical condition that, in the opinion of the
investigator, would compromise the safety of the patient or compromise the patient's
ability to participate in the study

- Previous hypersensitivity reaction to monoclonal antibodies

- Previous treatment with irinotecan, cetuximab, or any agent specifically targeting
IGF receptors

- Treatment with an investigational drug within 30 days prior to randomization

- Pregnancy or lactation at the time of patient entry

- Psychiatric or addictive disorders or other conditions that, in the opinion of the
investigator, would preclude the patient from meeting the study requirements