 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 109L, Platelets 100 x 109L, Hgb 9 gdl Total bilirubin 1.5 time the upper-normal limits UNL of the normal values and ASAT SGOT andor 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 mLmin 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 protein24 hr Will and ability to comply with the protocol Written informed consent to study procedures and to molecular analyses - 