Recent advances in biomarker-driven therapies have changed the landscape of unresectable metastatic colorectal cancer (mCRC) and brought not only access issues but also difficulties for the treating physician (especially generalist oncologists) in choosing the most suitable treatment for each individual patient. This manuscript proposes an algorithm developed by The Brazilian Group of Gastrointestinal Tumours with the aim of bringing easy-to-follow steps in the management of unresectable mCRC. The algorithm is based on evidence for fit patients to facilitate therapeutic decisions in the clinical practice and assumes that there are no access and resource limitations.