This is a randomised, multicentre observational study in patients suffering from RAS mutant mCRC with primarily unresectable metastases, who are planned to be treated with FOLFOXIRI and bevacizumab or who have already received ≤ four cycles FOLFOXIRI and bevacizumab as first-line treatment of metastatic disease. The patients are randomised in a 1:1 ratio to compare the rate of patients in whom secondary interventions (e.g. resection, ablation) are performed in curative intent when secondary intervention options are assessed by a multidisciplinary centralized tumour board (Arm A) versus when secondary intervention options are not assessed by a multidisciplinary centralized tumour board (Arm B).

All patients evaluated in the study will receive chemotherapy with FOLFOXIRI plus bevacizumab. After this induction/conversion therapy, imaging (CT or MRI) will be performed to evaluate resectability. In Arm A, a multidisciplinary, centralized tumour board will assess options of secondary intervention to be performed in the context of a generally curative treatment approach.

If there are secondary intervention options according to the judgement of the centralized tumour board, they will be listed in their respective sequence and the assessment will be communicated to the participating physician or his/her deputy at the study center. The decision, whether or not any secondary intervention is performed as recommended by the centralized tumour board as well as the kind of interventional procedures is up to the discretion of the treating physicians and surgeons of each patient. Any secondary intervention is recorded.

Evaluating the primary endpoint, the first interventions performed in one organ (e.g. liver) are rated when performed in a generally curative context (e.g. even in the presence of lung metastases that need to be approached in a further intervention).

In Arm B, no centralized tumour board will be integrated in to clinical decision making and patients will be treated according to institutional guidelines.

The number of treatment cycles with FOLFOXIRI and bevacizumab will be according to local clinical routine and medical guidelines, recommended are 8 to 12 cycles FOLFOXIRI in combination with bevacizumab, followed by a maintenance therapy with fluoropyrimidine (FP) plus bevacizumab until progression.

Inclusion Criteria:

1. Written informed consent to participate in the study

2. Patients ≥ 18 years at the time of signing the informed consent

3. Histologically confirmed (in primary tumour or metastasis) UICC stage IV metastatic adenocarcinoma of the colon or rectum (mCRC) with primarily unresectable metastases

4. RAS mutant CRC (as determined by local pathology in tissue of primary tumour or metastasis)

5. At least one measurable lesion according to RECIST version 1.1 in a CT/MRI scan performed within 28 days prior to start of systemic treatment (first cycle of induction treatment)

6. ECOG performance status 0-1

7. Patients planned to receive chemotherapy with FOLFOXIRI plus bevacizumab as first-line treatment of metastatic disease. De-escalation of FOLFOXIRI to FOLFIRI or FOLFOX is allowed in case of toxicity.

   Patients can also be included if they had already received ≤ 4 cycles of induction/conversion therapy with FOLFOXIRI plus bevacizumab (including those patients in whom FOLFOXIRI has been de-escalated to FOLFIRI or FOLFOX due to toxicity) and the first restaging has not been conducted prior to randomization.

8. Completion of adjuvant therapy for colorectal cancer > 3 months prior to start of systemic treatment (first cycle of induction treatment).

9. Patient's ability for treatment with FOLFOXIRI and bevacizumab according to participating physician's judgement.

Exclusion Criteria:

1. Pregnant or breast-feeding women. Females of childbearing potential (FCBPs) who do not practice adequate contraceptive measures as required according to SmPCs of the administered medicinal products.
2. Contraindication to intensive chemotherapy with FOLFOXIRI plus bevacizumab
3. Contraindications to treatment with 5-FU, oxaliplatin, folinic acid, irinotecan (FOLFOXIRI) and/or bevacizumab according to SmPCs of the administered medicinal products.
4. Patients with confirmed cerebral metastasis. In case of clinical suspicion of brain metastasis, a cranial CT or MRI must be performed to rule out brain metastasis before study inclusion.
5. Documentation of > 5 lung metastases (however, no limitation for the number of metastases in the liver)
6. Isolated distant nodal metastasis, isolated peritoneal metastasis or isolated bone metastasis
7. Limited legal capacity

Treatment naive patients with RAS mutated metastatic colorectal cancer who are planned to receive FOLFOXIRI plus bevacizumab or patients who already received up to 4 cycles of FOLFOXIRI plus bevacizumab.