Study in mCRC Patients RAS/BRAF wt Tissue and RAS Mutated LIquid BIopsy to Compare FOLFIRI Plus CetuxiMAb or BevacizumaB

Inclusion Criteria:

1. Provision of written informed consent;
2. Male or female \> 18 years of age;
3. Histologically confirmed diagnosis of colorectal adenocarcinoma RAS/BRAF wild type (analysed either on primary and/or related metastasis);
4. Initially unresectable metastatic colorectal cancer not previously treated with chemotherapy for metastatic disease;
5. Patient with left colorectal cancer;
6. Patients suitable for first line chemotherapy;
7. Life expectancy \> 3 months;
8. At least one site of measurable disease per RECIST criteria ver. 1.1;
9. ECOG Performance status = 2;
10. Adequate bone marrow, liver and renal function assessed before starting study treatment;
11. If DPD status is known it must be wild type. No restrictions are applied if DPD status in unknown;
12. Women of childbearing potential must have a negative blood pregnancy test within 24 hr prior to the start of study treatment. For this trial, women of childbearing potential are defined as all women after puberty, unless they are postmenopausal for at least 12 months, are surgically sterile, or are sexually inactive.
13. Subjects and their partners must be willing to avoid pregnancy during the trial and until 5 months for WOCBP (Women of Childbearing Potential) and 7 months for male subjects with female partners of WOCBP after the last trial treatment. Male subjects with female partners of childbearing potential and female subjects of childbearing potential must, therefore, be willing to use adequate contraception as approved by the investigator (barriers contraceptive measure or oral contraception).

Exclusion Criteria:

1. Previous chemotherapy treatment, with the exception of patient treated in adjuvant setting completed at least 6 months before the randomization;
2. Any contraindication to the use of Cetuximab, Bevacizumab, Irinotecan, 5FU or folinic acid;
3. Radiotherapy to any site within 4 weeks before the randomization;
4. Serious, non-healing wound, ulcer, or bone fracture;
5. Evidence of bleeding diathesis or coagulopathy;
6. Uncontrolled hypertension and prior history of hypertensive crisis or hypertensive encephalopathy;
7. Additional malignancy in the last 5 years. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy;
8. Active and untreated brain (CNS) metastases and/or carcinomatous meningitis;
9. Active infection requiring systemic therapy or active disseminated intravascular coagulation;
10. History of Human Immunodeficiency Virus (HIV) (HIV 1/2 antobodies);
11. Any positive test for hepatitis B or hepatitis C virus indicating acute or chronic infection;
12. Chronic, daily treatment with high-dose aspirin (\>325 mg/day);
13. Any previous venous thromboembolism \> NCI CTCAE Grade 3;
14. History of abdominal fistula, GI perforation, intra-abdominal abscess or active GI bleeding within 6 months prior to the first study treatment. History of acute or subacute intestinal occlusion or chronic inflammatory bowel disease or chronic diarrhoea;
15. Current, recent (within 10 days prior to study treatment start) or ongoing treatment with anticoagulants for therapeutic purposes;
16. 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;
17. History of any severe hypersensitivity reactions to any monoclonal antibody;
18. A significant concomitant disease which, in the investigating physician's opinion, rules out the patient's participation in the study