Abstract Colorectal cancer (CRC) still has a high prevalence of mortality in the world. So far, basic pre-clinical research based on 2D cultures has failed to improve patient prognostic outcomes. A growing field of research based on microphysiological systems (MPS) involvingorganoids/spheroids or patient-derived tumour cells has become a solid base for a better understanding of the tumour microenvironment and as a result a step towards personalized medicine. Furthermore, microfluidic approaches have also started to open possibilities of research, with tumour-on-chips and body-on-chips being used in order to decipher complex inter-organ signalling and the prevalence of metastasis, as well as CRC early-diagnosis through liquid biopsies. Herein, we focus on the state-of-the-art of CRC research with emphasis on 3D microfluidic in vitro cultures - organoids, spheroids – drug resistance, circulating tumour cells (CTCs) and microbiome-on-a-chip technology.