<p>Methyltransferase-like protein 3 (METTL3) functions as the primary “writer” of N6-methyladenosine (m6A), the most prevalent internal mRNA modification in eukaryotes. Functionally, METTL3 regulates a broad spectrum of cellular processes, including cell cycle progression, proliferation, apoptosis, invasion, migration, and differentiation. In colorectal cancer, METTL3 expression is frequently upregulated and has been correlated with poor prognosis. Therefore, this review attempts to organize and describe the main molecular and cellular mechanisms through which METTL3 drives colorectal cancer. Mechanistically, METTL3 contributes to tumor growth, metastatic dissemination, and the development of resistance to chemotherapy and radiotherapy. Special emphasis is placed on the clinical relevance of METTL3, not only as a biomarker, but also as a potential therapeutic target. Less explored topics are also addressed, such as the interaction between METTL3 and gut microbiota. Altogether, this review underscores the multifaceted role of METTL3 in colorectal cancer and the importance of further investigation to translate these insights into clinical applications.</p> Graphical abstract <p></p>