Inclusion Criteria:

1. Histologically or cytologically confirmed diagnosis of metastatic colorectal
adenocarcinoma

2. No prior chemotherapy for metastatic disease

3. Age ≥18 years

4. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (5. Life expectancy
> 3 months

5. Adequate organ function, including bone marrow (absolute neutrophil count (ANC)
≥l500/μl, haemoglobin ≥ 9g/dL, platelets ≥ 100,000/ μl); hepatic (total bilirubin <
1.6 mg/dl;SGOT and SGPT < 2.5 x upper limit of normal for patients without liver
metastases and < 5x upper limit of normal for patients with liver metastases); and
renal (serum creatinine ≤ 1.5x upper limit of normal).

6. Patients who are eligible to be registered in the study, based upon the above
criteria, will be genotyped for the UGT1A1*28 polymorphism and stratified into two
groups based on the presence of the UGT1A1*1/*1 or UGT1A1*1/*28 genotype.

7. Patients with the UGT1A1*28/*28 genotype or carriers of the other alleles (TA5 and
TA8)will be excluded.

8. For patients to be evaluable for response (a secondary end point), they must have at
least one measurable lesion as defined by RECIST (i.e., lesions that can be
accurately measured in at least one dimension with the longest diameter ≥ 20 mm using
conventional techniques or ≥ 10 mm using spiral CT scan).

9. Patients without measurable lesions can be included and will be evaluated only for
toxicity.

10. Signed informed consent and local IRB approval is required.

11. Women of child-bearing potential and men must agree to use adequate contraception
(hormonal or barrier method of birth control; abstinence) prior to study entry and
for the duration of study participation, up until 30 days after final study
treatment. Should a woman become pregnant or suspect that she is pregnant while
participating in this study, she should inform her treating physician immediately.

Exclusion Criteria:

1. Prior irinotecan or bevacizumab treatment

2. Inflammatory bowel disease (Crohn's disease, ulcerative colitis)

3. Diarrhea greater than grade 1

4. Bowel obstruction

5. Documented brain metastases

6. Serious active infectious disease

7. Active uncontrolled bleeding or fistulas

8. Pregnancy

9. Radiotherapy or major surgery within 4 weeks

10. Previous or concurrent malignancy, except for adequately treated basal cell or
squamous cell skin cancer, in situ cervical cancer, or any other cancer for which the
patient has been disease-free for five years.