- Background and rationale: approximately a quarter of the patients with synchronous metastatic colorectal cancer have metastases that are located in the peritoneum. Approximately half of these patients have peritoneal and other sites of metastases, whereas the other half has 'isolated' colorectal peritoneal metastases. The majority of the patients with isolated colorectal peritoneal metastases do not qualify for curative intent surgery, frequently due to extensive intraperitoneal disease. In these incurable patients, the toxicity and relative inefficacy of palliative systemic therapy have encouraged the development of intraperitoneal palliative therapies with a potentially similar or higher locoregional efficacy and a lower side-effect profile. Repeated laparoscopic Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC) is such an innovative therapy that has revealed encouraging preliminary toxicity and efficacy outcomes in patients with end-stage peritoneal metastases of various origins. Based on this preliminary evidence, oxaliplatin should be the preferred cytotoxic agent for repeated laparoscopic PIPAC for colorectal peritoneal metastases. Additionally, an intravenous bolus 5-fluorouracil/leucovorin may potentiate the efficacy of intraperitoneal oxaliplatin. Although repeated laparoscopic PIPAC with oxaliplatin is increasingly used in several European countries, sound scientific data on its safety, feasibility, tolerability, and oncological efficacy remain scarce. Therefore, this study investigates the safety, feasibility, tolerability, and preliminary oncological efficacy of upfront repeated laparoscopic PIPAC with oxaliplatin (92 mg/m2) and simultaneous intravenous bolus 5-fluorouracil/leucovorin (400/20 mg/m2) for isolated unresectable colorectal peritoneal metastases.