We introduce a new class of operators in any theory with a 't Hooft large-N limit that we call colour-twist operators. They are defined by twisting the colour-trace with a global symmetry transformation and are continuously linked to standard, un-twisted single-trace operators. In particular, correlation functions between operators that are twisted by an R-symmetry of N=4 SYM extend those in the γ-deformed theory. The most general deformation also breaks the Lorentz symmetry but preserves integrability in the examples we consider. In this paper, we focus on colour-twist operators in the fishnet model. We exemplify our approach for the simplest colour-twist operators with one and two scalar fields, which we study non-perturbatively using field-theoretical as well as integrability methods, finding a perfect match. We also propose the quantisation condition for the Baxter equation appearing in the integrability calculation in the fishnet model. The results of this paper constitute a crucial step towards building the separation of variable construction for the correlation functions by means of the Quantum Spectral Curve approach.