The scheme is part of the company's Railway Upgrade Plan and will replace equipment installed in the 1960s and 70s with modern technology.
In addition, it will also prepare the Great Western Main Line for the arrival of electrification and a new fleet of electric trains.
Other works include doubling of the tracks from two to four along the Filton bank to help improve capacity.
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The project will take place from 28 – 30 May and is the penultimate stage of the project known as the 'Filton Diamond re-signalling programme'.
Over 250km of new signalling and power cables has already been installed on the programme.
The work will require a temporary closure of the lines in both directions.
Andy Haynes, Network Rail's project director for the west of England, said: "This project forms part of our programme to re-signal the whole of the Great Western route, providing passengers with greater reliability, fewer delays and smoother journeys.
"Replacing and upgrading 40-year-old signalling equipment is complex and for safety reasons must be carried out when trains aren't running."
The final stage of the re-signalling project is due to take place over the August bank holiday, when control of the signalling system will be switched to the modern Thames Valley signalling centre in Didcot.
(LM/CD)
