Computational methods for protein structure modelling are routinely used to complement experimental structure determination, thus they help to address a broad spectrum of scientific questions in biomedical research. The most accurate methods today are based on homology modelling, i.e. detecting a homologue to the desired target sequence that can be used as a template for modelling. Here we present a versatile open source homology modelling toolbox as foundation for flexible and computationally efficient modelling workflows. ProMod3 is a fully scriptable software platform that can perform all steps required to generate a protein model by homology. Its modular design aims at fast prototyping of novel algorithms and implementing flexible modelling pipelines. Common modelling tasks, such as loop modelling, sidechain modelling or generating a full protein model by homology, are provided as production ready pipelines, forming the starting point for own developments and enhancements. ProMod3 is the central software component of the widely used SWISS-MODEL web-server.