Triplets of irinotecan, oxaliplatin and infusional 5-fluorouracil(FU)/leucovorin (LV) are associated with high response rates and long survival as first-line treatment for metastatic colorectal cancer (mCRC). The oral fluoropyrimidine, capecitabine, is better tolerated and shows better response rates than 5-FU/LV in metastatic colorectal cancer. A phase I dose-escalation study established dose limiting toxicity (DLT), maximum tolerated dose (MTD) and recommended phase II doses (RPIID) of irinotecan, oxaliplatin and capecitabine. This phase I /II study is to determine dose-limiting toxicities (DLTs), maximum tolerated dose (MTD), phase II recommended dose (RD) of IXO and bevacizumab combination and safety at the RD in an expanded cohort.

Inclusion Criteria:

• Histologically documented adenocarcinoma of the colon or rectum.
• Advanced and/or metastatic disease, incurable with standard therapy.
• Unresectable advanced and/or metastatic unidimensionally measurable disease (RECIST scale).
• Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2
• Age: over 18 years.
• Adequate haematological, renal and hepatic functions
• Patient consent must be obtained according to local REB requirements.
• Patients must be accessible for treatment and follow up.

Exclusion Criteria:

• Previous or concurrent malignancies
• Pregnant or lactating women. Women of childbearing potential must have had a negative pregnancy test within 7 days prior to registration.
• Concurrent treatment with other experimental drugs or anticancer therapy.
• Previous chemotherapy for advanced and/or metastatic disease.
• Previous adjuvant therapy with irinotecan or oxaliplatin.
• Previous full dose curative pelvic radiation therapy.
• Patients with documented brain metastases.
• Serious illness or medical condition.
• Gilbert's disease
• Use of enzyme inducing anticonvulsants such as phenytoin, phenobarbital and carbamazepine