The PROMETCO study is collecting real-world data on metastatic colorectal cancer (mCRC) patients with two progressions. This international, prospective, longitudinal, observational cohort study is collecting data on mCRC patients with two disease progressions since diagnosis and receiving subsequent treatment. Objectives include overall survival, treatment patterns, effectiveness and safety and patient-reported outcomes using the EuroQol 5-level, 5-dimensional questionnaire, the Brief Fatigue Inventory and a modified version of the ACCEPTance by the Patients of their Treatment (ACCEPT C) questionnaire. Data are collected retrospectively and prospectively up to 18 months. As of 13 October 2021, 544 patients from 18 countries had been enrolled. To the authors' knowledge, PROMETCO is the first international, real-world study of the continuum of care of mCRC patients in this setting. Trial registration number: NCT03935763 (ClinicalTrials.gov)