The main purpose of this study is to demonstrate the superiority of S 95005 in combination with bevacizumab over capecitabine in combination with bevacizumab.

Inclusion Criteria:

1. Has definitive histologically confirmed adenocarcinoma of the colon or rectum (all other histological types are excluded). Primary tumour localisation must be known.

2. RAS status based on local biological assessment of tumour biopsy must be available. If RAS status is not available at the time of randomisation, tumour biopsy must be available for RAS status determination (based on local biological assessment).

3. Patient is not a candidate for standard full dose combination chemotherapy with irinotecan or oxaliplatin

4. Patient is not a candidate for curative resection of metastatic lesions.

5. No previous systemic anticancer therapy for unresectable metastatic colorectal cancer.

6. ECOG (Eastern Cooperative Oncology Group) performance status ≤2.

7. Adequate organ function (renal, haematological, hepatic, coagulation) as described in the study protocol'

   Exclusion Criteria:

8. Pregnancy, breastfeeding or possibility of becoming pregnant during the study.

9. Participation in another interventional study within 4 weeks prior to the randomisation .

10. Patients who have not recovered from clinically relevant non-hematologic CTCAE grade ≥ 3 toxicity of previous anticancer therapy prior to the randomisation.

11. Symptomatic central nervous system metastases.

12. Major surgery within 4 weeks prior to the randomisation.

    Exclusion criteria related to S 95005 administration:

13. History of allergic reactions attributed to compounds of similar composition to S 95005 or any of its excipients.

14. Any contraindication present in the SmPC of trifluridine/tipiracil

    Exclusion criteria related to bevacizumab administration:

15. Any contraindication present in the SmPC of bevacizumab

    Exclusion criteria related to capecitabine administration:

16. Any contraindication present in the SmPC of capecitabine

Qualified scientific and medical researchers can request access to anonymized patient-level and study-level clinical trial data.

Access can be requested for all interventional clinical studies:

• used for Marketing Authorization (MA) of medicines and new indications approved after 1 January 2014 in the European Economic Area (EEA) or the United States (US).
• where Servier is the Marketing Authorization Holder (MAH). The date of the first MA of the new medicine (or the new indication) in one of the EEA Member States will be considered for this scope.

In addition, access can be requested for all interventional clinical studies in patients:

• sponsored by Servier
• with a first patient enrolled as of 1 January 2004 onwards
• for New Chemical Entity or New Biological Entity (new pharmaceutical form excluded) for which development has been terminated before any Marketing authorization (MA) approval.

After Marketing Authorisation in EEA or US if the study is used for the approval.

Researchers should register on Servier Data Portal and fill in the research proposal form. This form in four parts should be fully documented. The Research Proposal Form will not be reviewed until all mandatory fields are completed.