We review clinical data for late-line treatment options in patients with mCRC, including treatment options in unselected patients and therapies that should only be offered in patients with distinct tumor profiles, e.g., patients harboring BRAF mutations, KRAS G12C mutations, HER2 amplification, deficient MMR, or NRTK fusions, with a focus on randomized trials when available. Here, ERBB2 is linked to neoplasm.