Folfiri/aflIbercept in Metastatic coloreCTal Cancer patIents With RAS Validated Wild typE Status

Inclusion Criteria: * • Histological confirmation of colorectal cancer * Confirmed RAS wild type patient treated with an oxaliplatin-anti EGFR treatment in 1st line * At least one lesion measurable with CT or MRI scan * Radiologically documented progression while on or after discontinuation of treatment with FOLFOX in combination with an anti-EGFR monoclonal antibody (either cetuximab or panitumumab) * Radiologically documented progressing disease after FOLFOX in combination with an anti-EGFR monoclonal antibody (either cetuximab or panitumumab) * Life expectancy plus 3 months * Netrophils count ³ 1.5 x 109/L * Platelets count ³ 100 x 109/L * Hemoglobin ³ 9 g/dL * Creatinine £ 1.5 mg/dL, Proteinuria \<2+ (dipstick urinalysis) or ≤1g/24hour.Bilirubin £ 1.5 x ULN * AST and ALT £ 2.5 x ULN (\< 5 ULN in case of liver metastases) * Informed written consent * ECOG Performance Status \< 2 * Age plus18 yrs * Regular follow-up feasible. * For female patients of childbearing potential, negative serum pregnancy test within 1 week (7 days) prior of starting study treatment, * Female patients must commit to using reliable and appropriate methods of contraception until at least six months after the end of study treatment Exclusion Criteria: * • Concomitant protocol unplanned antitumor therapy (e.g. chemotherapy, molecular targeted therapy, immunotherapy), * Treatment with any other investigational medicinal product within 28 days prior to First Study treatment. * Other serious and uncontrolled non-malignant disease, * History or evidence upon physical examination of CNS metastasis unless adequately treated * Gilbert's syndrome * Intolerance to atropine sulfate or loperamide * Known dihydropyrimidine dehydrogenase deficiency * Treatment with CYP3A4 inducers unless discontinued \> 7 days prior to First Study treatment. * Any of the following in 3 months prior to inclusion: grade 3-4 gastrointestinal bleeding (unless due to resected tumor), treatment resistant peptic ulcer disease, erosive esophagitis or gastritis, infectious or inflammatory bowel disease, or diverticulitis. * Other concomitant or previous malignancy, except: i/ adequately treated in-situ carcinoma of the uterine cervix, ii/ basal or squamous cell carcinoma of the skin, iii/ cancer in complete remission for \>5 years, * Major surgery or traumatic injury within the last 28 days or until the surgical wound is fully healed whichever came later * Pregnant or breastfeeding women, * Patients with known allergy to any excipient to study drugs, * Bowel obstruction. * Uncontrolled infections * Known drugs or alcohol abuse * History of severe cardiovascular disease within 6 months prior to First Study treatment Uncontrollable hypertension, when treated with three or more drugs.