['metastatic colorectal cancer']
['fluoruracil', 'oxaliplatin', 'irinotecan', 'bevacizumab']

        Main Inclusion Criteria:

        Histologically proven diagnosis of colorectal cancer Initially unresectable metastatic
        colorectal cancer not previously treated with chemotherapy for metastatic disease At least
        one measurable lesion according to RECIST1.1 criteria Availability of a tumoral sample Male
        or female of 18-75 years of age ECOG PS < or = 2 if aged < 71 years, ECOG PS = 0 if aged
        71-75 years Life expectancy of at least 12 weeks Previous adjuvant chemotherapy allowed
        only if with fluoropyrimidine monotherapy and more than 6 months elapsed between the end of
        adjuvant and first relapse Neutrophils >1.5 x 109/L, Platelets >100 x 109/L, Hgb >9 g/dl
        Total bilirubin 1.5 time the upper-normal limits (UNL) of the normal values and ASAT (SGOT)
        and/or ALAT (SGPT) <2.5 x UNL (or <5 x UNL in case of liver metastases) alkaline
        phosphatase <2.5 x UNL (or <5 x UNL in case of liver metastases) Creatinine clearance >50
        mL/min or serum creatinine 1.5 x UNL Urine dipstick of proteinuria <2+. Patients discovered
        to have 2+ proteinuria on dipstick urinalysis at baseline, should undergo a 24-hour urine
        collection and must demonstrate <1 g of protein/24 hr Will and ability to comply with the
        protocol Written informed consent to study procedures and to molecular analyses -

        Main Exclusion Criteria:

        Radiotherapy to any site within 4 weeks before the study Previous adjuvant
        oxaliplatin-containing chemotherapy Previous treatment with bevacizumab Untreated brain
        metastases or spinal cord compression or primary brain tumours History or evidence upon
        physical examination of CNS disease unless adequately treated Symptomatic peripheral
        neuropathy > 2 grade NCIC-CTG criteria Serious, non-healing wound, ulcer, or bone fracture
        Evidence of bleeding diathesis or coagulopathy Uncontrolled hypertension and prior histor
        of hypertensive crisis or hypertensive encephalopathy Clinically significant (i.e. active)
        cardiovascular disease for example cerebrovascular accidents (≤6 months), myocardial
        infarction (≤6 months), unstable angina, New York Heart Association (NYHA) grade II or
        greater congestive heart failure, serious cardiac arrhythmia requiring medication
        Significant vascular disease (e.g. aortic aneurysm requiring surgical repair or recent
        arterial thrombosis) within 6 months of study enrolment Any previous venous thromboembolism
        > NCI CTCAE Grade 3 History of abdominal fistula, GI perforation, intra-abdominal abscess
        or active GI bleeding within 6 months prior to the first study treatment.

        Current or recent (within 10 days prior to study treatment start) ongoing treatment with
        anticoagulants for therapeutic purposes Chronic, daily treatment with high-dose aspirin
        (>325 mg/day) Treatment with any investigational drug within 30 days prior to enrollment or
        2 investigational agent half-lives (whichever is longer) Other co-existing malignancies or
        malignancies diagnosed within the last 5 years with the exception of localized basal and
        squamous cell carcinoma or cervical cancer in situ Major surgical procedure, open biopsy,
        or significant traumatic injury within 28 days prior to study treatment start, or
        anticipation of the need for major surgical procedure during the course of the study Lack
        of physical integrity of the upper gastrointestinal tract, malabsorption syndrome, or
        inability to take oral medication
      