This is a Phase II study of the drug combination of Oxaliplatin, Avastin and capecitabine. This is an open-label study.

Ongoing clinical trials are now evaluating the addition of bevacizumab to standard chemotherapeutic regimens for colorectal cancer such as FOLFOX or FOLFIRI. In these studies the addition of bevacizumab has been safe and has not resulted in significantly increased toxicity. Our proposed regimen has the advantage of being easily administered in the outpatient setting, with potential for enhanced activity and needs to be evaluated in a clinical trial.

The patterns of care for CRC have shifted, IFL previously the standard of care, is now proven to be an inferior regimen compared to FOLFOX4. (8) The recent FDA approval in February 2004 of bevacizumab for first line therapy, which states that bevacizumab is an approved agent in combination with a 5-FU regimen, gives no clear guidelines as to the "best regimen". This is an issue that needs to be evaluated rapidly in clinical trials, and it is clear that a combination of 5-FU or capecitabine with oxaliplatin and bevacizumab is one of the most active and well-tolerated regimens. The optimum sequence, schedule and doses needs to determined in clinical trials.

Inclusion Criteria:

• advanced, surgically unresectable CRC
• measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension(histological confirmation of adenocarcinoma of the colon or rectum.

ECOG performance status of 0, 1, or 2 Estimated life expectancy of at least 12 weeks.

• chemotherapy prior to the diagnosis of metastatic disease. The chemotherapy regimen must not have included oxaliplatin or bevacizumab. No prior therapy for metastatic disease is permitted.
• Evidence of adequate organ function, including:
• Evidence of adequate hepatic function,
• Evidence of adequate renal function INR <1.5 x ULN (unless taking warfarin in which case it must be in the therapeutic range). Patients on warfarin are allowed to participate.
• Absence of proteinuria on urine analysis· Patients with a history of prior non-colorectal malignancies are eligible if they have been disease-free for at least 5 years prior to study entry and are deemed by the physician to be at low risk for recurrence. Patients with the following cancers are eligible if diagnosed and treated within the past 5 years: melanoma in situ, and basal cell and squamous cell carcinoma of the skin.
• Age > 18 yrs.

Exclusion Criteria:

• Any systemic therapy administered for metastatic or locally recurrent disease. Patients who are considered candidates for surgical resection of metastatic and/or locally advanced disease.
• Any histology other than adenocarcinoma of the colon or rectum.
• Pregnancy or lactation at the time of patient entry or women of childbearing potential with no pregnancy test. Eligible patients of reproductive potential (both sexes) must agree to use adequate contraceptive methods during and for 6 months after study therapy.
• Serious concomitant medical conditions that, in the opinion of the investigator, would compromise the safety of the patient or compromise the patient's ability to complete the study.
• General Medical Concerns History of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that might affect the interpretation of the results of the study or render the subject at high risk from treatment complications.
• Serious, uncontrolled, concurrent infection.
• Lack of physical integrity of the upper gastrointestinal tract or malabsorption syndrome.
• Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 0, or anticipation of need for major surgical procedure during the course of the study; fine needle aspirations or core biopsies within 7 days prior to Day 0.
• Proteinuria at baseline or clinically significant impairment of renal function.
• Serious, non healing wound, ulcer, or bone fracture
• Subjects who can not take oral medication