• E. faecalis down-regulates MOB3B expression in colorectal cancer cells, promoting chemoresistance.
• MOB3B overexpression reduces cell viability and reverses chemoresistance to oxaliplatin and 5-fluorouracil.
• MOB3B modulates chemoresistance in an LRRC19-dependent manner, linking the Hippo pathway to drug resistance.
• Low MOB3B expression correlates with high Tumour Regression Grade, indicating its potential as a prognostic and chemosensitivity marker.