• Measurable metastatic CRC based on RECIST v1.1;

• The primary tumor has been resected before study inclusion or the patient is asymptomatic with respect to the in situ primary tumor;

• Last imaging ≤ 4 weeks prior to the on-study ablative procedure;

• Age ≥ 18 years;

• Eastern Cooperative Oncology Group (ECOG) performance status of no more than 1;

• A life expectancy of at least 3 months at the time of inclusion;

• Adequate bone marrow, liver, and renal function as assessed by laboratory tests. These results should be judged by the local investigator and should be conducted within 7 days prior to definite inclusion;

• Written informed consent.

• Progressive or stable metastatic CRC on CT-scan after at least 1 lines of standard of care systemic treatment. Standard of care systemic treatment will be defined and determined by the treating oncologist. A summary of standard of care systemic treatment for CRLM as used by the medical oncologists at Amsterdam UMC has been listed in Table 1. Patients can also be included if systemic treatment has to be terminated due to toxicity or when patients refuse (further) systemic treatment, or when patients are in a therapy break from systemic therapy as patients can continue with further systemic treatment one month after the study treatment;

• At least 2 CRLM eligible for MWA with a minimum diameter of 1cm and a maximum diameter of 3cm and one (optional but not required) CRLM that will be left untreated and is eligible for biopsy;

• No limitations on intrahepatic or extrahepatic disease;

• At least one CRLM and a maximum of three CRLM size ≤ 3 cm eligible for MWA with curative intent;

• Additional unablatable CRLM should be resectable with a maximum of 10 additional CRLM;

• Resectability and ablatability should be re-confirmed intra-operatively by US in case of combined/staged resection and ablation. Intra-operatively also full exploration for hepatic, peritoneal and regional lymph node metastases should be performed;

• Liver only or liver dominant measurable metastatic CRC based on RECIST v1.1;

• Liver dominant metastatic disease is defined as the hepatic tumorload (number and estimated volume) exceeding the extrahepatic tumorload, with a maximum of 5 unequivocal extrahepatic metastases in ≤2 different organ systems;

• At least 2 CRLM, of which at least one is eligible for the study treatment (RFA, MWA and IRE);

• At least 50% (number and estimated volume) of the CRLM should be eligible for ablation. A maximum of 4 CRLM can be assigned for the study treatment. One CRLM has to be left untreated;

• At least one untreated CRLM and one 'to-be-treated' CRLM should be eligible for biopsy;

• Maximum size of CRLM for study treatment is 3cm;

• Any CRLM with a maximum lesion size of 5cm at time of inclusion;

• Limited extrahepatic disease, restricted to the lungs and lymph nodes, with a maximum lesion size of 3cm at time of inclusion. See below for additional information regarding pulmonary nodules;

• Progressive disease on CT-scan after standard of care systemic treatment. Standard of care systemic treatment will be defined and determined by the treating oncologist. Patients can also be included if systemic treatment has to be terminated due to toxicity or when patients refuse (further) systemic treatment.;