The REVERT project will address the specific challenge of understanding at system level the pathophysiology of mCRC cancer in patients responding well or poorly to therapies, in order to design optimal strategy for mCRC on a case by case basis, with therapeutic interventions modulated depending on patient’s features. Accordingly, REVERT will build up an innovative artificial intelligence (AI)-based decision support system using the experience and the real-world data of several general Hospitals operating in the EU healthcare system ultimately aimed at developing an improved and innovative model of combinatorial therapy - based on a personalised medicine approach - that identifies the most efficient and cost-effective therapeutic intervention for patients with unresectable mCRC. This goal will be pursued through the building of the REVERT-DataBase (RDB) thanks to a large number of standardized biobank samples with related structured data, and clinical databases (including known clinical and biological features as well as new, potential prognostic/predictive biomarkers) from several major clinical European centres. The RDB, in turn, will be used to build a sophisticated computational framework based on AI to evaluate its impact on survival and quality of life in a prospective clinical trial through testing of new treatment sequences of the available and authorised molecular targeted drugs in patients with mCRC. In the end, the REVERT will also generate an EU- network among SMEs, Research Institutions, Clinical Centres and Biobanks focused on R&D in the field of AI-Health for the development of personalised medicine. The REVERT software system will ensure the integrity of data and privacy management in respect to national rules, the EU's GDPR (Reg. EU 2016/679) and the EU Charter of Fundamental Rights. The RDB and AI services will be open to all partners during and after project’s completion, available also to EU research Institutions for future studies.