Inclusion Criteria:

- Histologically confirmed colorectal adenocarcinoma

- Unresectable and measurable metastatic disease (RECIST criteria)

- Male or female, aged > 18 years and ≤ 75 years

- ECOG Performance Status (PS) < 2 if aged < 71 years

- ECOG PS = 0 if aged 71-75 years

- Life expectancy of more than 3 months

- Adequate haematological function: ANC ≥ 1.5 x 109/L; platelets ≥ 100 x 109/L, Hb ≥ 9
g/dL

- INR ≤ 1.5 and aPTT ≤ 1.5 x ULN within 7 days prior to starting study treatment

- Adequate liver function: serum bilirubin ≤ 1.5 x ULN; alkaline phosphatase and
transaminases ≤ 2.5 x ULN (in case of liver metastases < 5 x ULN)

- Serum Creatinine ≤ 1.5 x ULN

- Urine dipstick for proteinuria < 2+. If urine dipstick is ≥ 2+, 24- hour urine must
demonstrate ≤ 1 g of protein in 24 hours

- Previous adjuvant chemotherapy is allowed if more than 12 months have elapsed between
the end of adjuvant therapy and first relapse

- At least 6 weeks from prior radiotherapy and 4 weeks from surgery

Exclusion Criteria:

- Prior palliative chemotherapy

- Prior treatment with bevacizumab

- Bowel obstruction (or subobstruction)

- History of inflammatory enteropathy or extensive intestinal resection (>
hemicolectomy or extensive small intestine resection with chronic diarrhea)

- Symptomatic peripheral neuropathy > 2 grade NCIC-CTG criteria

- Presence or history of CNS metastasis

- Active uncontrolled infections

- Active disseminated intravascular coagulation

- Major surgical procedure, open biopsy or significant traumatic injury within 28 days
prior to treatment, or anticipation of the need for major surgery during the course
of the study

- Central Venous Access Device (CVAD) for chemotherapy administration inserted within 2
days prior to study treatment start

- Past or current history of malignancies other than colorectal carcinoma, except for
curatively treated basal and squamous cell carcinoma of the skin cancer or in situ
carcinoma of the cervix

- Clinically significant cardiovascular disease, for example cerebrovascular accidents
(CVA) (≤ 6 months before treatment start), myocardial infarction (≤ 6 months before
treatment start), unstable angina, NYHA ≥ grade 2 chronic heart failure (CHF),
uncontrolled arrhythmia

- Uncontrolled hypertension

- 24-hour urine protein > 1 g if dipstick > 2+

- History of thromboembolic or hemorrhagic events within 6 months prior to treatment

- Evidence of bleeding diathesis or coagulopathy

- Serious, non healing wound/ulcer or serious bone fracture

- No therapeutic anticoagulation or antiplatelet agents or NSAID with anti-platelet
activity (aspirin ≤ 325 mg/day allowed)

- Pregnancy or lactation

- Fertile women (< 2 years after last menstruation) and men of childbearing potential
not willing to use effective means of contraception