FOLFOX-4 regimens consist of 85 mg/m2 oxaliplatin plus 200 mg/m2 LV and 5-FU 400 mg/m2 bolus on day 1 followed by 1600 mg/m2 5-FU as a 46-h infusion

Bevacizumab according to standard of care

Assessed with the 5-level EQ-5D by EuroQol group (EQ-5D-5L) at baseline, one week after the first cycle, one week after the fourth cycle, one week after the eighth cycle, and one week after the twelfth cycle. The EQ-5D-5L essentially consists of 2 pages: the EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS).The descriptive system comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems. The digits for the five dimensions can be combined into a 5-digit number that describes the patient's health state.The EQ VAS records the patient's self-rated health on a vertical visual analogue scale, where the endpoints are labelled 'The best health you can imagine' and 'The worst health you can imagine'. The VAS can be used as a quantitative measure of health outcome that reflect the patient's own judgement.

Assessed with the European Organization for Research and Treatment for Cancer Quality of Life Questionnaire (EORTC QLQ-C30) at baseline, one week after the first cycle, one week after the fourth cycle, one week after the eighth cycle, and one week after the twelfth cycle. The EORTC QLQ-C30 comprises 30 items, 24 of which are aggregated into nine multi-item scales, that is, five functioning scales, three symptom scales and one global health status scale. The remaining six single-item assess symptoms. All of the scales and single-item measures range in score from 0 to 100. Higher score for the functioning scales and global health status denote a better level of functioning (i.e. a better state of the patient), while higher scores on the symptom and single-item scales indicate a higher level of symptoms (i.e. a worse state of the patient).

Assessed with the European Organization for Research and Treatment for Cancer Quality of Life Questionnaire, specifically for colorectal cancer (EORTC QLQ-CR29) at baseline, one week after the first cycle, one week after the fourth cycle, one week after the eighth cycle, and one week after the twelfth cycle. The resulting QLQ-CR29 consisted of four scales and 19 individual items. Higher scores indicate a higher level of symptoms (i.e. a worse state of the patient).

According to the Dutch manual for cost analysis in health care research, and assessed with the iMTA Medical Consumption Questionnaire at baseline, one week after the first cycle, one week after the fourth cycle, one week after the eighth cycle, and one week after the twelfth cycle. The volumes of used healthcare costs were multiplied with the unit costs of these corresponding services.

Assessed with the iMTA Productivity Cost Questionnaire at baseline, one week after the first cycle, one week after the fourth cycle, one week after the eighth cycle, and one week after the twelfth cycle.

Assessed during standard-of-care laboratory assessment for nephrotoxicity (creatinine, eGFR, and ureum) analysis before each subsequent cycle and graded according to Common Terminology Criteria for Adverse Events (CTCAE, version 5.0).

Assessed during standard-of-care laboratory assessment for hepatotoxicity (albumin, bilirubin, AST, ALT, LD, AF, yGT) analysis before each subsequent cycle and graded according to Common Terminology Criteria for Adverse Events (CTCAE, version 5.0).

Assessed during standard-of-care laboratory assessment for haematological toxicity (haemoglobin, leucocytes, thrombocyte) analysis before each subsequent cycle and graded according to Common Terminology Criteria for Adverse Events (CTCAE, version 5.0).

Assessed by carcino-embryonic antigen (CEA) analysis during standard laboratory analysis before each subsequent cycle

To determine the number of patients completing twelve cycles of treatment with intraperitoneal irinotecan (75 mg) and concomitant palliative systemic therapy, required dose reductions, and reasons for discontinuation.

assessed by thoracoabdominal CT at baseline, after the fourth cycle, after the eighth cycle, and after the twelfth cycle according to RECIST.

To determine the the peritoneum/plasma ratio of intraperitoneal during the first and fourth cycle of intraperitoneal irinotecan (75 mg) and concomitant palliative systemic therapy. Whole blood and peritoneal fluid will be drawn from a peripheral intravenous access and the peritoneal access port, respectively, and collected in 3 mL lithium heparin tubes and 2 mL cryotubes, respectively, at the following moments after the start of irinotecan infusion; t=0, at the end of infusion (EOI), t=30 minutes after EOI and t =2 hrs after EOI and t = 4hrs after EOI. The ratio between the Area Under the Curve (AUC) between irinotecan measured in the peritoneum and measured in the plasma is taken.