AbstractBackgroundColorectal cancer is the third most common cancer and second leading cause of cancer mortality in Australia, thus carrying a significant disease burden.AimsThis analysis aims to explore real‐world treatment landscape of metastatic colorectal cancer in the third‐line setting.MethodsWe retrospectively analysed treatment of recurrent and advanced colorectal cancer (TRACC) registry database from 2009 onwards. Patients treated with palliative intent who progressed after two lines of therapies were included. One treatment line was defined as any combination of systemic therapy given until progression.ResultsOut of 1820 patients treated palliatively, 32% (590 patients) met study criteria. Of these, 43% (254 patients) proceeded to third‐line therapy, equating to 14% of all metastatic patients. In KRAS mutant or unknown tumours (97 patients), fluoropyrimidine (FP)‐oxaliplatin combination was the most common choice (51%), followed by FP‐irinotecan (15%), trifluridine/tipiracil (11%), mono‐chemotherapy (10%), regorafenib (5%) and others (7%). Majority of FP‐doublet (83%) was given as rechallenge. In 157 patients with KRAS wildtype disease, monotherapy with EGFR inhibitor was most commonly used (41%), followed by EGFR inhibitor with chemotherapy (20%), FP‐doublet (18%), mono‐chemotherapy (6%), trifluridine/tipiracil (6%), regorafenib (1%) and others (8%). Median overall survival was 7.1 months (range 0.4‐41.2), and median time on third‐line treatment was 3 months (range 0.1‐40).ConclusionsIn real‐world Australian population, treatment choices differed based on KRAS status and will likely change with the availability of newer drugs on the pharmaceutical benefits scheme. Survival outcomes are comparable to newer agents in clinical trials for select patients.