Trial in Metastatic Colorectal Cancer With FOLFIRI Plus Aflibercept as First Line Treatment

Inclusion Criteria: * Patients with histologically documented adenocarcinomas of colon or rectum with unresectable metastatic disease. * No prior treatment for metastatic disease * Metastatic liver disease assessable with diffusion-weighted Magnetic Resonance Imaging (MRI) * No previous treatment with bevacizumab or Cetuximab or Panitumumab. * Patients may have receive fluoropyrimidines with or without oxaliplatin as adjuvant treatment, if they have progressed \> 12 months after the end of the last cycle of the adjuvant treatment * Performance Status (ECOG) 0-2 * Life expectancy ≥ 3 months. * Effective contraception for both male and female subjects if the risk of conception exists. * Adequate laboratory parameters: Absolute neutrophils count ≥ 1.5 x 109 /L, Platelets ≥ 100 x 109 /L, Leucocytes \> 3,000/mm; Hemoglobin\> 10.5g/dl, creatinine clearance ≥ 60 ml/min, Proteinuria \<2+ (dipstick urinalysis) or ≤1g/24hour, Magnesium ≥ lower limit of normal, Calcium ≥ lower limit of normal, total Bilirubin ≤ 1.5 times the upper limit of normal; aspartate and alanine aminotransferase ≤ 3 times of the upper normal limit in absence of liver metastases, or ≤5x Upper Normal Limits (UNL) in presence of liver metastases, alkaline phosphatases \< 5x UNL * All patients will have to sign written informed consent in order to participate in the study. * Female patients must commit to using reliable and appropriate methods of contraception until at least three months after the end of study treatment (when applicable). Male patients with a partner of childbearing potential must agree to use contraception in addition to having their partner use another contraceptive method during the trial Exclusion Criteria: * Known hypersensitivity reaction to the component of the treatment. * Inability to underwent a diffusion-weighted MR Imaging at baseline and in predefined time points * Subject pregnant or breast feeding, or planning to become pregnant within 6 months after the end of treatment. * History or evidence upon physical examination of Central Nervous System (CNS) metastasis unless adequately treated (e.g. non irradiated CNS metastasis, seizure not controlled with standard medical therapy), * Concomitant protocol unplanned antitumor therapy (e.g. chemotherapy, molecular targeted therapy, immunotherapy), * Treatment with any other investigational medicinal product within 28 days prior to study entry. * Other serious and uncontrolled non-malignant disease * Uncontrolled hypertension (defined as systolic blood pressure \>150 mmHg and/or diastolic blood pressure \>100 mmHg), or history of hypertensive crisis, or hypertensive encephalopathy. * Gilbert's syndrome * Intolerance to atropine sulfate or loperamide * Known dihydropyrimidine dehydrogenase deficiency * Treatment with CYP3A4 inducers unless discontinued \> 7 days prior to randomization * 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 * Any other serious and uncontrolled non-malignant disease, major surgery or traumatic injury within the last 28 days * INR in absence of anticoagulation therapy \> 1.25 or poorly controlled anti-coagulation therapy on coumadin or heparin compounds (INR \>3.0) * History of myocardial infarction and/or stroke within 6 months prior to randomization, New York Heart Association (NYHA) class III and IV congestive heart failure * History of life threatening (grade 4) venous thromboembolic events (including pulmonary embolism) within 6 months prior to registration, * Bowel obstruction * Legal incapacity or limited legal capacity. * Medical or psychological condition which in the opinion of the investigator would not permit the subject to complete the study or sign meaningful informed consent. * A second primary tumour other than non-melanoma skin cancer or in situ cervical cancer. * History of interstitial lung disease e.g. pneumonitis or pulmonary fibrosis or evidence of interstitial lung disease on chest CT scan.